Creatine Supplements May Help Treat Depression, Early Evidence Shows

• A large review suggests that creatine could be an adjunct treatment for major depressive disorder (MDD).
• However, not all studies in the review found the same benefits for treating depression symptoms with creatine.
• Those with depression who would like to try creatine should continue with existing treatments, using it only as an add-on.
• Experts note that creatine supplements have an excellent safety profile when taken as directed.
• Lifestyle choices such as good sleep, exercise, nutrition, and stress management can also protect brain health.

Creatine monohydrate, a popular dietary supplement commonly used by athletes and fitness enthusiasts to build muscle, could serve as an adjunct treatment for depression.

A large systematic review explored the potential benefits of creatine for mental health. 

Researchers from the University of Ottawa and the University of Toronto analyzed randomized controlled trials (RCTs) conducted worldwide and found that creatine supplementation shows promise for improving symptoms of major depressive disorder (MDD).

Their findings, however, are mixed, highlighting the need for further large-scale studies. The results were published in Brain Medicine on June 30.

Depression affects around 332 million people worldwide, according to the World Health Organization (WHO).

As the review authors highlight, many people experience only partial or no response to depression medications, making it essential to explore other treatment options.

The authors say that creatine, known for its role in cellular energy metabolism, may help by providing an energy buffer for brain cells. This is particularly relevant, they add, because impaired energy metabolism and mitochondrial dysfunction have been linked to depression.

Evidence for creatine as depression treatment

The researchers examined the effects of creatine monohydrate supplementation on mental health conditions, focusing mainly on mood disorders. 

The review included five RCTs with a total of 238 participants: 126 received creatine supplementation, and 112 received a placebo. 

The average age was 36 years, and the majority of participants were female; two of the five trials enrolled only women.

Supplementation doses varied between studies, ranging from 2 grams to 10 grams per day, with treatment durations typically lasting from 4 to 8 weeks. 

Some trials investigated creatine as an add-on to pharmacological treatments such as antidepressants, while others combined it with cognitive behavioral therapy (CBT). 

The researchers assessed depressive symptoms using standard clinical scales like the Hamilton Depression Rating Scale and the Patient Health Questionnaire.

Due to variations in the studies, including differences in creatine dosage, length of treatment, and participant characteristics, the team summarized the findings in narrative form rather than performing a meta-analysis.

They also noted that some clinical trial data were unavailable, limiting the overall assessment.

Mixed evidence on creatine and depression

The review found mixed evidence that creatine can help treat depression when used alongside standard care.

Two papers based on the same clinical trial found promising results in women with major depressive disorder who took 5 grams of creatine daily in addition to the antidepressant escitalopram (Lexapro).

After eight weeks, those taking creatine had greater improvements in depression symptoms and were more likely to go into remission than those taking a placebo.

Another study found that people receiving creatine alongside CBT experienced greater symptom improvement than those who received CBT with a placebo.

On the other hand, other studies found little or no benefit. One trial involving people whose depression had not improved with antidepressants found that adding creatine did not reduce symptoms after four weeks.

Another study in teenage girls with depression found no meaningful differences between several creatine doses and a placebo after eight weeks.

A third study involving people with bipolar disorder also found no benefit, and two participants taking creatine developed hypomania or mania, suggesting it should be used cautiously in people with bipolar disorder.

Across the studies, creatine was generally well tolerated, with only mild digestive side effects reported.

However, most participants were female, and the studies were relatively small, making it difficult to know whether the findings apply to the broader population.

The authors further noted that animal research suggests creatine may affect males and females differently, which could help explain why study results have varied.

They say there are several reasons creatine could help relieve depression. It helps the brain produce and replenish energy needed for normal cell function and may also affect brain chemicals involved in regulating mood, including dopamine and serotonin.

Overall, the researchers concluded that creatine shows promise as an add-on treatment for major depressive disorder, but the evidence remains inconsistent.

They found no studies examining creatine for mental health conditions other than mood disorders and say larger, longer-term studies involving more diverse groups of people are needed to determine who, if anyone, is most likely to benefit.

Creatine as an add-on therapy for depression

Barry K. Herman, MD, a double board certified psychiatrist as well as Chief Medical Officer at Mentavi Health, said that while this is an interesting area of research, the evidence isn’t currently strong enough to recommend it as a stand-alone treatment for depression. Herman wasn’t involved in the study.

Instead, people who are interested in trying it should take it as a supplement alongside their existing treatment.

Additionally, Herman advised speaking with your healthcare professional first, especially if you have kidney disease, bipolar disorder, or are taking multiple medications.

“More importantly, depression is not a single disorder, but a highly heterogeneous condition with many potential contributing factors,” said Herman. “Before adding supplements, patients should first receive a comprehensive evaluation to ensure an accurate diagnosis and that proven treatments have been optimized.”

David Perlmutter, MD, a board certified neurologist and author of the soon-to-be-released book “Brain Defenders,” noted, however, that creatine has been widely studied, and, for healthy people, it has a very good safety profile when taken as recommended.

“Higher doses have not consistently produced better outcomes,” he added, “and the goal should never be to megadose in hopes of accelerating benefits.”

Perlmutter, who wasn’t involved in the study, advised choosing a reputable brand that offers pure creatine monohydrate, as that is the form most extensively studied.

Finally, he suggested incorporating supplementation into an overall brain health strategy.

“The lifestyle choices that consistently have the greatest impact on brain health remain regular exercise, restorative sleep, good nutrition, stress management, and maintaining metabolic health,” said Perlmutter. “Those interventions also improve mitochondrial function and reduce inflammation.”